The incidence of esophageal adenocarcinoma has been rising rapidly over the past two decades for unclear reasons. The most important risk factor for this cancer is Barrett's esophagus, a metaplastic condition in which the squamous mucosa of the esophagus is replaced by a specialized columnar epithelium in response to acid-, and possibly bile-reflux. Approximately 10% of individuals with chronic gastroesophageal reflux disease develop Barrett's esophagus and 0.5% of those with this condition progress to cancer annually. Nonetheless, there has been little systematic research into understanding the risk factors for Barrett's metaplasia. The candidate for this award proposes to use the resources of a large, ongoing, prospective cohort study, the Nurses' Health Study, to identify potential modifiable risk factors such as body mass index, cigarette and alcohol use, non-steroidal anti-inflammatory drug use, and dietary habits. The prospective collection of exposure information prior to disease diagnosis removes the biases inherent in retrospective studies and provides a unique investigative opportunity to clarify associations between various exposures and the development of Barrett's esophagus. Completion of this project will improve our understanding of this common pre-malignant condition and perhaps provide further insight into its pathogenesis. In addition, this project will allow the candidate to gain invaluable experience in database analysis and clinical epidemiology. The candidate will undergo formal coursework in nutritional epidemiology and advanced biostatistics. The research will be performed under the mentorship of Dr. Charles Fuchs and Dr. M. Michael Wolfe, well-established investigators in health-services research. At the completion on the project, the candidate will have gained the experience to become an independent researcher in clinical epidemiology.